Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis

Proteostasis Therapeutics

Status and phase

Completed

Phase 2

Phase 1

Conditions

Cystic Fibrosis

Treatments

Drug: Placebo

Drug: PTI-428

Drug: PTI-801

Drug: PTI-808

Study type

Interventional

Funder types

Industry

Identifiers

NCT03500263

PTI-808-02

Details and patient eligibility

About

The study is a randomized, double-blind, placebo-controlled, study that will be conducted at multiple centers in subjects with Cystic Fibrosis (CF) who are either homozygous for the F508del mutation or heterozygous with at least copy of the F508del mutation.

Full description

Study PTI-808-02 will enroll up to approximately 32 subjects. Subjects in the first cohort will receive PTI-808 and PTI-801. Following completion of Cohort 1, initiation of enrollment into subsequent cohorts will be based upon review and approval by the Safety Review Committee (SRC).

Enrollment

12 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Cohorts 1,2 and 4: A Confirmed diagnosis of CF with the F508del/F508del CFTR genotype on record, along with clinical findings consistent with CF such as chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities
Cohort 3 only: Confirmed diagnosis of CF with at least one copy of the F508del CFTR mutation on record, along with clinical findings consistent with CF, such as chronic sinopulmonary disease or gastrointestinal / nutritional abnormalities
Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive
Non-smoker and non-tobacco user for a minimum of 30 days prior to screening
Cohort 3 only: A sweat chloride value of ≥60 mmol/L based on quantitative pilocarpine iontophoresis (as documented in the subject's medical record or as confirmed at the screening visit)

Exclusion criteria

Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of study drugs
Participation in another clinical trial or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1
History of cancer within the past 5 years
History of organ transplantation
Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (as determined by the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 14 days of Day 1
Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline, azithromycin, Pulmozyme®, Cayston®, TOBI®) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1
History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
Pregnant or nursing women

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

12 participants in 6 patient groups, including a placebo group

Cohorts 1 and 2: PTI-808 Active Co-admin with PTI-801 Active

Active Comparator group

Description:

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.

Treatment:

Drug: PTI-801

Drug: PTI-808

Cohorts 1 and 2: PTI-808 Placebo Co-admin with PTI-801 Placebo

Placebo Comparator group

Description:

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.

Treatment:

Drug: Placebo

Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active

Active Comparator group

Description:

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.

Treatment:

Drug: PTI-428

Drug: PTI-801

Drug: PTI-808

Cohort 3 PTI-808 placebo + PTI-801 Placebo + PTI-428 Placebo

Placebo Comparator group

Description:

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.

Treatment:

Drug: Placebo

Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active

Active Comparator group

Description:

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.

Treatment:

Drug: PTI-428

Drug: PTI-801

Drug: PTI-808

Cohort 4 PTI-808 Placebo + PTI-801 Placebo + PTI-428 Placebo

Placebo Comparator group

Description:

Treatment:

Drug: Placebo